Making Knowledge Work for Health: A Strategy for Health Research

Making Knowledge Work for Health: A Strategy for Health Research, provides a framework for the development of health research to enhance health and quality of life and help ensure that our research compares favourably with the rest of the world. I believe that an active research community working close to the delivery of health care in clinical settings, laboratories, the community, third-level institutions and the healthcare industry is critical to the improvement of the quality of health services generally. It is vital for professional development and career satisfaction of health service staff. It is also important for the translation of ideas into medical and IT products that can add value to our economy Download the Report here

Neutrophil-derived CCL3 is essential for the rapid recruitment of dendritic cells to the site of Leishmania major inoculation in resistant mice.

Neutrophils are rapidly and massively recruited to sites of microbial infection, where they can influence the recruitment of dendritic cells. Here, we have analyzed the role of neutrophil released chemokines in the early recruitment of dendritic cells (DCs) in an experimental model of Leishmania major infection. We show in vitro, as well as during infection, that the parasite induced the expression of CCL3 selectively in neutrophils from L. major resistant mice. Neutrophil-secreted CCL3 was critical in chemotaxis of immature DCs, an effect lost upon CCL3 neutralisation. Depletion of neutrophils prior to infection, as well as pharmacological or genetic inhibition of CCL3, resulted in a significant decrease in DC recruitment at the site of parasite inoculation. Decreased DC recruitment in CCL3(-/-) mice was corrected by the transfer of wild type neutrophils at the time of infection. The early release of CCL3 by neutrophils was further shown to have a transient impact on the development of a protective immune response. Altogether, we identified a novel role for neutrophil-secreted CCL3 in the first wave of DC recruitment to the site of infection with L. major, suggesting that the selective release of neutrophil-secreted chemokines may regulate the development of immune response to pathogens.

Five new CYLD mutations in skin appendage tumors and evidence that aspartic acid 681 in CYLD is essential for deubiquitinase activity.

Brooke-Spiegler syndrome, familial cylindromatosis, and familial trichoepithelioma are autosomal-dominant genetic predispositions for benign tumors of skin appendages caused by mutations in the CYLD gene localized on chromosome 16q12-q13. The encoded protein functions as ubiquitin-specific protease (UBP), which negatively regulates NF-kappaB and c-Jun N-terminal kinase (JNK) signaling. We investigated five families affected with these skin neoplasms and identified four premature stop codons and the novel missense mutation D681G in a family in which 11 of 12 investigated tumors were trichoepitheliomas. CYLD protein harboring this missense mutation had a significant reduced ability to inhibit TNF receptor-associated factor (TRAF)2- and TRAF6-mediated NF-kappaB activation, tumor necrosis factor-alpha (TNFalpha)-induced JNK signaling, and to deubiquitinate TRAF2. CYLD-D681G was coimmunoprecipitated by TRAF2, but was unable to cleave K63-linked polyubiquitin chains. Aspartic acid 681 is highly conserved in CYLD homologues and other members of the UBP family, but does not belong to the Cys and His boxes providing the CYLD catalytic triad (Cys601, His871, and Asp889). As reported previously, the homologous residue D295 of HAUSP/USP-7 forms a hydrogen bond with the C-terminal end of ubiquitin and is important for the enzymatic activity. These results underline that D681 in CYLD is required for cleavage of K63-linked polyubiquitin chains.

Rôle de l'exercice dans l'approche multidisciplinaire de la lombalgie chronique

RÉSUMÉ L'exercice est utilisé dans le traitement de la lombalgie depuis plus de cent ans. La recherche dans ce domaine a commencé au milieu du XXème siècle puis s'est développée exponentiellement jusqu'à nos jours. La première étude de cette thèse a eu pour but de passer en revue cette abondante littérature scientifique. Il en est ressorti que l'exercice est un moyen efficace de prévention primaire et secondaire de la lombalgie. En tant que modalité de traitement, l'exercice permet de diminuer l'incapacité et la douleur et d'améliorer la condition physique et le statut professionnel des patients lombalgiques subaigus et chroniques. Parmi les caractéristiques de l'exercice, la supervision est essentielle. Des investigations ultérieures sont nécessaires afin d'identifier des sous-groupes de patients répondant favorablement à d'autres caractéristiques de l'exercice. L'exercice est souvent utilisé dans l'optique de maintenir les résultats obtenus à la suite d'un traitement, bien que peu d'études s'y soient penchées. La deuxième partie de cette thèse a eu pour objectifs d'évaluer l'efficacité d'un programme d'exercice (PE) suivi par des patients lombalgiques chroniques ayant complété une restauration fonctionnelle multidisciplinaire (RFM), en comparaison avec le suivi classique (SC) consistant simplement à encourager les patients à adopter un quotidien aussi actif que possible par la suite. Les résultats ont montré que les améliorations obtenues au terme de RFM étaient maintenues par les deux groupes à un an de suivi. Bien qu'aucune différence n'ait été obtenue entre les deux groupes, seul le groupe PE améliorait significativement l'incapacité et l'endurance isométrique des muscles du tronc. Une analyse économique a ensuite été réalisée afin d'évaluer la rentabilité de PE. L'évaluation de la qualité de vie des patients au terme de RFM et à un an de suivi permettait d'estimer les années de vie ajustées par leur qualité (QALYs) gagnées par chaque groupe. Les coûts directs (visites chez le médecin, spécialiste, physio, autres) et indirects (jours d'absence au travail) étaient estimés avant RFM et à un an de suivi à l'aide d'un agenda. Aucune différence significative n'était obtenue entre les groupes. Une mince différence de QALYs en faveur de PE ne se traduisait néanmoins pas en bénéfices mesurables. La recherche future devrait s'attacher à identifier un ou des sous-groupe(s) de patients pour lesquels SC ne permet pas de maintenir à long terme les améliorations obtenues au terme de RFM, et pour lesquels l'efficacité thérapeutique et la rentabilité économique de PE pourraient être accrues. ABSTRACT Exercise is used to treat low back pain for over a hundred years. Research in this area began in the mid-twentieth century and then grew exponentially until nowadays. The first study of this thesis was aimed to review this abundant scientific literature. It showed that exercise is effective in the primary and secondary prevention of low back pain. As a modality of treatment, exercise can reduce disability and pain and improve physical fitness and professional status of patients with subacute and chronic low back pain. Among different exercise characteristics, supervision is essential. Further investigations are needed to identify subgroups of patients responding positively to other characteristics of exercise. Exercise is often used as a post-treatment modality in order to maintain results over time, although only a few studies addressed this issue directly. The purpose of the second part of this thesis was to evaluate the effectiveness of an exercise program (EP) for patients with chronic low back pain who completed a functional multidisciplinary rehabilitation (FMR), compared to the routine follow-up (RF) which simply consisted of encouraging patients to adopt an active daily life thereafter. The results showed that improvements obtained at the end of FMR were maintained by both groups at one year follow-up. Although no difference was obtained between both groups, only the EP group significantly improved disability and isometric endurance of trunk muscles. An economic analysis was then carried out to assess the cost-effectiveness of EP. Based on the evaluation of patients' quality of life after FMR and at one year follow-up, an estimation of adjusted life years for their quality (QALYs) gained by each group was done. Direct costs (physician, specialist, physiotherapist, other therapists visits) and indirect costs (days off work) were measured before FMR and at one year follow-up using a cost diary. No significant difference was obtained between both groups. A slight difference in QALYs in favour of EP did yet not translate into measurable benefits. Future research should focus on identifying subgroups of patients for which RF is insufficient to reach long-term improvements after FMR, and for which the therapeutic effectiveness and cost-effectiveness of EP could be increased.

Work and health : remodelling perspectives of working life research, as proposed by Järvholm et al. (2009)

Järvholm and Co-workers (2009) proposed a conceptual model for research on working life. Models are powerful communication and decision tools. This model is strongly unidirectional and does not cover the mentioned interactions in the arguments.With help of a genealogy of work and of health it is shown that work and health are interactive and have to be analysed on the background of society.Key words: research model, work, health, occupational health, society, interaction, discussion paperRemodellierung der von Järvholm et al. (2009) vorgeschlagenen Forschungsperspektiven in Arbeit und GesundheitJärvholm und Kollegen stellten 2009 ein konzeptionelles Modell für die Forschung im Bereich Arbeit und Gesundheit vor. Modelle stellen kraftvolle Kommunikations- und Entscheidungsinstrumente dar. Die Einflussfaktoren im Modell verlaufen jedoch nur in einer Richtung und bilden die interaktiven Argumente im Text nicht ab. Mit Hilfe einer Genealogie der Begriffe Arbeit und Gesundheit wird aufgezeigt, dass Arbeit und Gesundheit sich gegenseitig beeinflussen und nur vor dem Hintergrund der jeweiligen gesellschaftlichen Kontextfaktoren zu analysieren sind.Introduction : After an interesting introduction about the objectives of research on working life, Järvholm and Co-workers (2009) manage to define a conceptual model for working life research out of a small survey of Occupational Safety and Health (OSH) definitions. The strong point of their model is the entity 'working life' including personal development, as well as career paths and aging. Yet, the model Järvholm et al. (2009) propose is strangely unidirectional; the arrows point from the population to working life, from there to health and to disease, as well as to productivity and economic resources. The diagram only shows one feed-back loop: between economic resources and health. We all know that having a chronic disease condition influences work and working capacity. Economic resources have a strong influence on work, too. Having personal economic resources will influence the kind of work someone accepts and facilitate access to continuous professional education. A third observation is that society is not present in the model, although this is less the case in the arguments. In fact, there is an incomprehensible gap between the arguments brought forth by Järvholm and co-workers and their reductionist model.Switzerland has a very low coverage of occupational health specialists. Switzerland is a long way from fulfilling the WHO's recommendations on workers' access to OSH services as described in its Global plan of action. The Institute for Work and Health (IST) in Lausanne is the only organisation which covers the major domains of OSH research that are occupational medicine, occupational hygiene, ergonomic and psychosocial research. As the country's sole occupational health institution we are forced to reflect the objectives of working life research so as not to waste the scare resources available.I will set out below a much shortened genealogy of work and of health, with the aim of extending Järvholm et al's (2009) analyses on the perspectives of working life research in two directions. Firstly towards the interactive nature of work and health and the integration of society, and secondly towards the question of what working life means or where working life could be situated.Work, as we know it today - paid work regulated by a contract as the basis for sustaining life and as a base for social rights - was born in modern era. Therefore I will start my genealogy in the pre-modern era, focus on the important changes that occurred during industrial revolution and the modern era and end in 2010 taking into account the enormous transformations of the past 20-30 years. I will put aside some 810 years of advances in science and technology that have expanded the world's limits and human understanding, and restrict my genealogy to work and to health/body implicating also the societal realm. [Author]

An Integrated Work Force Planning Strategy For The Health Services 2009 - 2012

An Integrated Work Force Planning Strategy For The Health Services 2009 – 2012 Click here to download PDF 1.6mb

RadA protein from Archaeoglobus fulgidus forms rings, nucleoprotein filaments and catalyses homologous recombination.

Proteins that catalyse homologous recombination have been identified in all living organisms and are essential for the repair of damaged DNA as well as for the generation of genetic diversity. In bacteria homologous recombination is performed by the RecA protein, whereas in the eukarya a related protein called Rad51 is required to catalyse recombination and repair. More recently, archaeal homologues of RecA/Rad51 (RadA) have been identified and isolated. In this work we have cloned and purified the RadA protein from the hyperthermophilic, sulphate-reducing archaeon Archaeoglobus fulgidus and characterised its in vitro activities. We show that (i) RadA protein forms ring structures in solution and binds single- but not double-stranded DNA to form nucleoprotein filaments, (ii) RadA is a single-stranded DNA-dependent ATPase at elevated temperatures, and (iii) RadA catalyses efficient D-loop formation and strand exchange at temperatures of 60-70 degrees C. Finally, we have used electron microscopy to visualise RadA-mediated joint molecules, the intermediates of homologous recombination. Intriguingly, RadA shares properties of both the bacterial RecA and eukaryotic Rad51 recombinases.

Promoting physical activity at work: A guide for employers

This booklet is the second in a series of short guides aimed at promoting health in the workplace. It outlines to employers the benefits of promoting physical activity at work, how workplaces can be active places through simple activities and changes, what information and facilities can benefit employees,

Breastfeeding and returning to work

This leaflet aims to encourage breastfeeding mothers to continue breastfeeding after they have returned to work. It highlights the benefits of continuing to breastfeed, sets out the options for combining breastfeeding and work, explains the rights breastfeeding mothers have to support from their employer, and outlines what facilities and equipment mothers will need to express milk at work.

Promoting breastfeeding for mothers returning to work: a guide for employers

This booklet is the third in a series of Work Well guides aimed at promoting health in the workplace. It outlines to employers the business benefits of encouraging mothers to continue breastfeeding on return to work, the health benefits of breastfeeding for mums, the legislation affecting mothers at work, and some easy steps that employers can take to support breastfeeding mothers.